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Risk factors for cytomegalovirus (CMV) acquisition in men having sex with men remain unclear. Seroprevalence, incidence, risk factors and shedding of CMV were analyzed among participants enrolled in the HIV pre-exposure prophylaxis IPERGAY-ANRS trial. Among the 417 participants tested, 382 were seropositive at baseline (prevalence of 91.6%; 95%CI[88.5–94.1]) and 10/35 seroconverted during the study (incidence of 17.1 per 100 person-years; 95%CI[8.2–31.3]). A high number of sexual partners was independently associated with CMV seroprevalence. Shedding among CMV-seroconverters was reported for 6/9 and 2/9 at the oral and anal levels, respectively. Our data supports transmission of CMV during sexual contacts. Study part of the ANRS-IPERGAY Clinical trial ClinicalTrials.gov number, NCT01473472. [ABSTRACT FROM AUTHOR]

Introduction: Daily pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on-demand PrEP with TDF/FTC in HIV-1 uninfected men. Methods: We used data from the randomized double-blind placebo-controlled ANRS-IPERGAY trial and its open-label extension conducted between February 2012 and June 2016 among HIV-uninfected MSM starting on-demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. Results: During the blind phase, with a median follow-up of 9.4 months, the mean decline slope of eGFR from baseline was -0.88 and -1.53 mL/min/1.73 [m.sup.2] per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 [m.sup.2] per year (p = 0.27). Including both phases, 389 participants started on-demand TDF/FTC with a median follow-up of 19.2 months and a mean decline of eGFR from baseline of -1.14 mL/min/1.73 [m.sup.2] per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR [less than or equal to] 90 mL/min/1.73 [m.sup.2] (p = 0.44), age >40 years (p = 0.24) or hypertension (p = 0.21). There was a dose-response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of -0.88 mL/min/1.73 [m.sup.2] between >15 pills/month vs. [less than or equal to]15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to [less than or equal to]2 ng/mL: >2 to [less than or equal to]10ng/mL: -0.98 mL/min/1.73 [m.sup.2], >10 to [less than or equal to]40ng/mL: -1.28 mL/min/1.73 [m.sup.2], >40 ng/mL: -1.82 mL/min/1.73 [m.sup.2], p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 [m.sup.2] during the OLE phase. No case of Fanconi syndrome was reported. Conclusions: The renal safety of on-demand PrEP with TDF/FTC was good. The overall reduction and intermittent exposure to TDF/FTC may explain this good renal safety. Keywords: PrEP; on-demand; intermittent; kidney; eGFR; tenofovir; HIV, 1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)--emtricitabine (FTC) raises a lot of expectations to hamper HIV epidemic due to its high effectiveness to prevent HIV acquisition [...]

Introduction: In the SMART trial, baseline plasma hsCRP, IL6 and D‐dimer levels were strongly correlated to all‐cause mortality. A case‐control study has shown an increase of IL‐6 and D‐dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D‐dimer but not IL‐6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART‐experienced adults with plasma HIV RNA levels Methods: Stored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL‐6, sCD‐14, hsCRP and D‐dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL‐6, sCD14, hsCRP and D‐Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL‐6, hsCRP, sCD14 and D‐dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis. Results: At baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T‐cell count of 768/mm[sup.3], have received a median of 4.7 years of ART and 85% had HIV RNA Compared to baseline, D‐dimer levels significantly increased 8 weeks after ART interruption in the IT arm (+23% fold change, 95% CI +9% to +39%) but reverted to baseline levels at week 16 and remained unchanged at week 96. There was no significant change from baseline in the other biomarker levels in the IT arm. Similarly, no significant change from baseline in biomarker levels was seen in the CT arm up to 96 weeks. Conclusion: Coagulation and inflammatory biomarkers levels remained stable over 96 weeks in well‐suppressed HIV‐infected patient on ART. Following ART interruption there was a significant increase in D‐dimer but not in inflammatory biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption increases coagulation rather than inflammatory biomarkers., Table 1: Changes in biomarkers levels in participants from the intermittent (IT) vs continuous (CT) treatment arms through 96 weeks (*p=0.002, Wilcoxon test) IL‐6(pg/mL) sCD14(ng/mL) hsCRP(#x00B5;g/mL) D‐dimer(µg/mL) IT CT IT [...]

Background: In the ANRS EASIER trial where treatment-experienced patients switched from enfuvirtide (ENF) to raltegravir (RAL), a high incidence of transaminase elevation was reported in the RAL arm. Methods: We compared the incidence of emergent liver enzyme elevations (LEE) of grade 2 or more among patients randomized to the maintenance ENF arm or the switch RAL arm up to W24. We also assessed the overall incidence of LEE over the 48-week duration of the trial and baseline risk factors for grade 2 or more alanine aminotransferase (ALT) elevation using univariate and multivariate analyses. Results: During the first 24 weeks, 6/84 (7.1 %) and 2/85 patients (2.4%) presented with ALT elevation of grade 2 or more in the RAL and ENF arms, respectively (p = 0.21). Grade 2 or more γGT and ALP elevations were seen in 18 and 11 % (p = 0.35), and 5 and 1 % (p = 0.14) of patients in the RAL and ENF arms, respectively. The 48-week incidence of grade 2 or more LEE was 11.6 per 100-pts-years for ALT, 24.5 per 100-pts-years for γ-GT and 4.5 per 100-pts-years for ALP, respectively. In the multivariate analysis, tipranavir/ritonavir use (OR 3.66; 95 % Cl [1.20-11.1], p = 0.022) and elevated ALT at baseline (OR 10.3; 95 % Cl [2.67-39.6], p < 10-3) were significantly associated with a grade 2 or more ALT elevation during follow-up. Conclusion: The incidence of LEE was relatively high in these highly treatment-experienced patients switching to a RAL-based regimen. Both tipranavir/ritonavir use and high baseline ALT levels were associated with an increased risk of ALT. [ABSTRACT FROM AUTHOR]

We evaluated the impact of on-demand oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) on herpes simplex virus (HSV)-1/2 incidence among men who have sex with men (MSM) enrolled in the ANRS IPERGAY trial. Serum samples were tested at baseline and at the last visit for HSV-1/2 antibodies. Overall HSV-1 incidence was 11.7 per 100 person-years; 16.2 and 7.8 per 100 person-years in the TDF/FTC and placebo arm, respectively (P =.19). Overall HSV-2 incidence was 7.6 per 100 person-years; 8.1 and 7.0 per 100 person-years in the TDF/FTC and placebo arm, respectively (P =.75). On-demand oral PrEP with TDF/FTC failed to reduce HSV-1/2 incidence in this population. [ABSTRACT FROM AUTHOR]

Background: Incidence and risk factors for thrombocytopenia in patients discontinuing highly active antiretroviral therapy (HAART) have not been fully investigated., Methods: Well-suppressed patients on HAART were randomized to continuous (CT) or intermittent therapy (IT) for 96 weeks. Incidence of thrombocytopenia (<150 x 10(3) platelets/mm(3)) was assessed and multivariate analysis performed to identify baseline predictors. Correlations were assessed between platelet, CD4, CD8 T-cell counts, and viral load after treatment interruption., Results: Three hundred ninety-one patients were included, with a median baseline platelet count of 243,000/mm(3). The incidence of thrombocytopenia at week 96 was significantly higher in the IT versus the CT arm (25.4% versus 9.8%, respectively, P < 0.001) and median time to thrombocytopenia was 9 weeks. In multivariate analysis, the IT strategy: odds ratio (OR) = 4.1 (2.1-7.9; P < 0.0001), a history of thrombocytopenia: OR = 11.9 (2.4-57.9; P = 0.002), and a low baseline platelet count: OR = 3.4 (2.3-5.1; P < 0.0001) were associated with an increased risk of thrombocytopenia. Also, after treatment interruption, changes from baseline in platelet counts were correlated with changes in CD4 T-cell counts and plasma HIV RNA levels (P < 0.001 for both)., Conclusions: Intermittent therapy is associated with a high incidence of thrombocytopenia, especially among patients with low platelet counts and a history of thrombocytopenia.

Background: Structured treatment interruptions in chronic HIV infection have been explored as a drug-sparing strategy to reduce drug-related adverse events and costs while maintaining CD4 cell counts at a level high enough to prevent the risk of disease progression., Objectives: To test the hypothesis and put a figure on the reduction in total medical costs, we conducted a cost study analysis in the setting of a randomized open-label study comparing an intermittent to a continuous antiretroviral regimen., Patients and Methods: Four hundred three HIV-1-infected adults who were tolerating highly active antiretroviral therapy (HAART), with a nadir CD4 count of 100 cells per microliter or more and a CD4 count above 450 cells per microliter at screening, were randomly assigned to switch to a fixed 8-week off, 8-week on intermittent treatment (IT) or to maintain their current treatment (CT) strategy. The proportions of patients who reached a CD4 cell count below 300 cells per microliter through 96 weeks (primary end point) were not significantly different between arms. Costs were estimated from the viewpoint of the payer over the 96-week study period. Unit costs were provided from the national reimbursement schedules for hospital inpatient and outpatient admissions and ambulatory visits and the national selling price for medications. All analyses were performed on an intention-to-treat basis., Results: Complete cost data were available for 391 patients (197 patients in the IT and 194 in the CT arms). The mean cost in euros (Euro) per patient over the 96 weeks of follow-up (excluding protocol-driven costs) was 9738 in the IT arm vs. 16,162 in the CT arm, a 6424 difference almost entirely due to the difference in HAART cost. Mean protocol-driven costs represented Euro290 in the IT vs. Euro280 in the CT arm. The use of IT achieved a 40% reduction in the total cost of HAART., Conclusions: Reducing by 40% the cost ofHAART medications in a treatment interruption strategy did not increase the costs related to adverse events or consultations.

Background: Whether structured treatment interruptions (STIs) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy (HAART) in patients with primary HIV infection is controversial., Methods: In this multicenter, prospective trial, patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks. Afterward, patients with plasma viral load (PVL) <50 copies/mL entered the STI phase, which consisted of 3 consecutive periods of 2, 4, and 8 weeks off HAART, each separated by 12 weeks on HAART. HAART was permanently stopped at week 84 and patients were followed up for 24 weeks. The primary endpoint for definition of virologic success was a PVL <50 copies/mL during the 6 months following HAART discontinuation., Results: Of the 29 patients enrolled, 26 completed the trial. Six months after HAART discontinuation, only 1 patient (3.8%, 95% CI: 0.1% to 19.6%) had PVL <50 copies/mL, whereas 6 of 26 (23.1%, 95% CI: 9.0% to 43.7%) had PVL <1000 copies/mL. Female gender was the only parameter significantly associated with a PVL <1000 copies/mL. No other parameter, either at baseline or before HAART discontinuation, predicted virologic success at week 108. A major protease inhibitor resistance mutation (L90M) developed in 3 patients., Conclusions: This trial failed to confirm that a significant proportion of patients with primary HIV infection can maintain suppression of viremia after a sequence of HAART/STIs followed by HAART discontinuation.